KR20010023001A - 관절염 치료용 아그레카나제 및 기질 메탈로프로테나제의 신규 억제제 - Google Patents

관절염 치료용 아그레카나제 및 기질 메탈로프로테나제의 신규 억제제 Download PDF

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Publication number
KR20010023001A
KR20010023001A KR1020007001609A KR20007001609A KR20010023001A KR 20010023001 A KR20010023001 A KR 20010023001A KR 1020007001609 A KR1020007001609 A KR 1020007001609A KR 20007001609 A KR20007001609 A KR 20007001609A KR 20010023001 A KR20010023001 A KR 20010023001A
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KR
South Korea
Prior art keywords
hydroxy
phenyl
indanyl
methyl
butanediamide
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KR1020007001609A
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English (en)
Korean (ko)
Inventor
웬큉 야오
칼 피. 데시코
Original Assignee
블레어 큐. 퍼거슨
듀폰 파마슈티컬즈 컴퍼니
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Application filed by 블레어 큐. 퍼거슨, 듀폰 파마슈티컬즈 컴퍼니 filed Critical 블레어 큐. 퍼거슨
Publication of KR20010023001A publication Critical patent/KR20010023001A/ko

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
    • C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D257/04—Five-membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
    • C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
    • C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
    • C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C311/03—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C311/06—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
    • C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C311/08—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C311/21—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
    • C07D295/205—Radicals derived from carbonic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
    • C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
    • C07D317/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Rheumatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
KR1020007001609A 1997-08-18 1998-08-18 관절염 치료용 아그레카나제 및 기질 메탈로프로테나제의 신규 억제제 KR20010023001A (ko)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US5594497P 1997-08-18 1997-08-18
US60/055,944 1997-08-18
US6833597P 1997-12-19 1997-12-19
US60/068,335 1997-12-19
PCT/US1998/017048 WO1999009000A2 (en) 1997-08-18 1998-08-18 Novel inhibitors of aggrecanase and matrix metalloproteinases for the treatment of arthritis

Publications (1)

Publication Number Publication Date
KR20010023001A true KR20010023001A (ko) 2001-03-26

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KR1020007001609A KR20010023001A (ko) 1997-08-18 1998-08-18 관절염 치료용 아그레카나제 및 기질 메탈로프로테나제의 신규 억제제

Country Status (15)

Country Link
US (1) US6576664B1 (et)
EP (1) EP1005448A2 (et)
KR (1) KR20010023001A (et)
CN (1) CN1268117A (et)
AR (1) AR016134A1 (et)
AU (1) AU9021498A (et)
BR (1) BR9815596A (et)
CA (1) CA2301038A1 (et)
EE (1) EE200000093A (et)
HR (1) HRP980443A2 (et)
IL (1) IL133952A0 (et)
NO (1) NO20000784L (et)
PL (1) PL339006A1 (et)
SK (1) SK1602000A3 (et)
WO (1) WO1999009000A2 (et)

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US6747027B1 (en) 1996-07-22 2004-06-08 Pharmacia Corporation Thiol sulfonamide metalloprotease inhibitors
US6794511B2 (en) 1997-03-04 2004-09-21 G. D. Searle Sulfonyl aryl or heteroaryl hydroxamic acid compounds
US7115632B1 (en) 1999-05-12 2006-10-03 G. D. Searle & Co. Sulfonyl aryl or heteroaryl hydroxamic acid compounds
US6696449B2 (en) 1997-03-04 2004-02-24 Pharmacia Corporation Sulfonyl aryl hydroxamates and their use as matrix metalloprotease inhibitors
NZ503485A (en) 1997-11-14 2002-10-25 G Aromatic sulfone hydroxamic acid metalloprotease inhibitor
US6750228B1 (en) 1997-11-14 2004-06-15 Pharmacia Corporation Aromatic sulfone hydroxamic acid metalloprotease inhibitor
US20010039287A1 (en) 1997-11-14 2001-11-08 Thomas E Barta Aromatic sulfone hydroxamic acid metalloprotease inhibitor
US6800646B1 (en) 1999-02-08 2004-10-05 Pharmacia Corporation Sulfamato hydroxamic acid metalloprotease inhibitor
WO2000059285A2 (en) * 1999-04-02 2000-10-12 Du Pont Pharmaceuticals Company NOVEL LACTAM INHIBITORS OF MATRIX METALLOPROTEINASES, TNF-α, AND AGGRECANASE
US6649377B1 (en) 1999-05-10 2003-11-18 Syntex (U.S.A.) Llc Human aggrecanase and nucleic acid compositions encoding the same
US6656448B1 (en) * 2000-02-15 2003-12-02 Bristol-Myers Squibb Pharma Company Matrix metalloproteinase inhibitors
US6683093B2 (en) 2000-05-12 2004-01-27 Pharmacia Corporation Aromatic sulfone hydroxamic acids and their use as protease inhibitors
CA2446586A1 (en) 2001-05-11 2002-11-21 Thomas E. Barta Aromatic sulfone hydroxamates and their use as protease inhibitors
US6683078B2 (en) 2001-07-19 2004-01-27 Pharmacia Corporation Use of sulfonyl aryl or heteroaryl hydroxamic acids and derivatives thereof as aggrecanase inhibitors
AU2003221786A1 (en) 2002-04-25 2003-11-10 Pharmacia Corporation Piperidinyl-and piperazinyl-sulfonylmethyl hydroxamic acids and their use as protease inhibitors
WO2004053103A2 (en) * 2002-12-11 2004-06-24 University Of Massachusetts METHOD OF INTRODUCING siRNA INTO ADIPOCYTES
ATE464286T1 (de) 2003-12-15 2010-04-15 Japan Tobacco Inc Cyclopropanderivate und ihre pharmazeutische verwendung
WO2005108949A2 (en) * 2004-05-12 2005-11-17 Galapagos N.V. Methods, compositions and compound assays for inhibiting amyloid-beta protein production
RU2008137593A (ru) * 2006-02-22 2010-03-27 Вертекс Фармасьютикалз Инкорпорейтед (Us) Модуляторы мускариновых рецепторов
EP2146720A4 (en) * 2007-05-10 2012-01-18 Amr Technology Inc ARYLOXY- AND HETEROARYLOXY-SUBSTITUTED TETRAHYDROBENZAZEPINE AND THEIR USE FOR THE RECOURSE-INHIBITION OF NOREPINEPHRIN, DOPAMINE AND SEROTONINE
NZ596304A (en) * 2009-05-28 2014-01-31 Novartis Ag Substituted aminopropionic derivatives as neprilysin inhibitors
US20150023873A1 (en) 2011-11-11 2015-01-22 Lantheus Medical Imaging, Inc. Evaluation of presence of and vulnerability to atrial fibrillation and other indications using matrix metalloproteinase-based imaging
CA3121986C (en) * 2014-12-24 2024-04-09 Lg Chem, Ltd. Biaryl derivative as gpr120 agonist

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GB8827308D0 (en) 1988-11-23 1988-12-29 British Bio Technology Compounds
GB9102635D0 (en) 1991-02-07 1991-03-27 British Bio Technology Compounds
EP0586537A4 (en) 1991-05-28 1997-06-25 Merck & Co Inc Substituted n-carboxyalkylpeptidyl derivatives as antidegenerative active agents
US5413999A (en) * 1991-11-08 1995-05-09 Merck & Co., Inc. HIV protease inhibitors useful for the treatment of AIDS
US5318964A (en) 1992-06-11 1994-06-07 Hoffmann-La Roche Inc. Hydroxamic derivatives and pharmaceutical compositions
GB2268935B (en) 1992-06-24 1996-10-23 Nat Heart & Lung Inst Diagnosis of rejection of transplanted organs
GB9215665D0 (en) 1992-07-23 1992-09-09 British Bio Technology Compounds
GB9307956D0 (en) 1993-04-17 1993-06-02 Walls Alan J Hydroxamic acid derivatives
GB9320660D0 (en) 1993-10-07 1993-11-24 British Bio Technology Inhibition of cytokine production
US5508404A (en) * 1995-03-15 1996-04-16 Merck & Co., Inc. Reductive amination process
US6008243A (en) 1996-10-24 1999-12-28 Agouron Pharmaceuticals, Inc. Metalloproteinase inhibitors, pharmaceutical compositions containing them, and their use

Also Published As

Publication number Publication date
IL133952A0 (en) 2001-04-30
AR016134A1 (es) 2001-06-20
WO1999009000A3 (en) 1999-09-10
SK1602000A3 (en) 2000-09-12
AU9021498A (en) 1999-03-08
CA2301038A1 (en) 1999-02-25
PL339006A1 (en) 2000-12-04
WO1999009000A2 (en) 1999-02-25
EP1005448A2 (en) 2000-06-07
US6576664B1 (en) 2003-06-10
NO20000784D0 (no) 2000-02-17
HRP980443A2 (en) 1999-10-31
NO20000784L (no) 2000-04-07
BR9815596A (pt) 2001-01-02
CN1268117A (zh) 2000-09-27
EE200000093A (et) 2000-12-15

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